Drug site-specific

Controlled release, although resulting in a zero-order delivery system, may also incorporate methods to promote localization of the drug at an active site. In some cases, a controlled-release system will not be sustaining, but will be concerned strictly with localization of the drug. Site-specific systems and targeted-delivery systems are the descriptive terms used to denote this type of delivery control. 

The potential use of poloxamers in the medical field has been extensively investigated [5,35]. The use of poloxamers in drug delivery, as gels in the controlled release of drugs and in solid form in the targetting of drugs at specific sites in the body, has received significant atten-... 

Polymeric microparticles have been studied and developed for several years. Their contribution in the pharmacy field is of utmost importance in order to improve the efficiency of oral delivery of drugs. As drug carriers, polymer-based microparticles may avoid the early degradation of active molecules in undesirable sites of the gastrointestinal tract, mask unpleasant taste of drugs, reduce doses and side effects and improve bioavailability. Also, they allow the production of site-specific drug targeting, which consists of a suitable approach for the delivery of active molecules into desired tissues or cells in order to increase their efficiency. 

Davis, S. S., and Ilium, L. (1986). Colloidal delivery systems opportunities and challenges, in Site-Specific Drug Delivery (E. Tomlinson and S. S. Davis, eds.), John Wiley and Sons, Chichester, pp. 93-110. 

Poste, G., and Kirsh, R. (1983). Site-specific (targeted) drug delivery in cancer chemotherapy. Biotechnology, 1, 869-878. 

Tomlinson, E. (1987). Theory and practice of site-specific drug delivery, Adv. Drug Del. Rev.. 1, 87-198. 

Over the past decade, the use of polymers in drug delivciy systems has increased dramatically, particularly in site-specific or systematic administration of pharmaceutical agents. This timely reference reviews the properties, synthesis, and formulations of a variety of polymers. 

Tomlinson E. Davis S.S. (eds) (1986) Site Specific Drug Delivery. Chichester John Wiley. (This deals in part with monoclonal antibodies.)... 

Provide a specific interaction between the delivery and biological systems such as site-specific targeting, regional delivery, or localized delivery to improve the therapeutic index of a drug. 

One element that is often ignored in this evaluation though is the extent of the mechanism. For example, if enzymatic activity is to be used to release drug at the site of action, even if the activity/time/volume is one hundred times higher at the desired site than elsewhere (not unreasonable), but the volume of nonspecific activity is one thousand times as great (also not unreasonable), the system does not stand any chance of achieving site-specific delivery. 

Finally, site-specific delivery also depends on the extent of competing processes in the biological system as well as the interaction of the drug itself with the biological system. Therefore successful design of polymeric drug delivery approaches requires a comprehensive appreciation of the pharmacology, pharmacokinetics, and pharmacodynamics involved. 

Tomlinson, E. "Site specific drug delivery using multiparticulate systems", In Modern Pharmaceutics, Banker, G. S., Rhodes, C. T., Eds. Drugs and the Pharmaceutical Sciences M. Dekker, New York, NY, 1990, Vol. 40, pp. 673-694. 

PD Scholes, AGA Coombes, L Ilium, SS Davis, M Yert, MC Davies. The preparation of sub-200 nm poly (lactide-co-glycolide) microspheres for site-specific drug delivery. J Control Rel 25 145-153, 1993. 

In addition, biodegradable nanoparticles for sustained release formulations to improve site-specific drug delivery has also been reviewed [98]. 

Table 1 Reasons for Site-Specific Delivery of Drugs Pharmaceutical...

Numerous reports of prodrugs in the literature show improved drug effects. Prodrugs that have shown some measure of success for site-specific delivery include L-3,4-dihydroxyphenylalanine (L-dopa) to the brain [56], dipivaloyl derivative of epinephrine to the eye [57], /-glutamyl-L-dopa to the kidney [58], fi-n-glucoside dexamethasone and prednisolone derivatives to the colon [59], thiamine-tetrahydrofuryldisulfide to red blood cells, and various amino acid derivatives of antitumor agents such as daunorubicin [61,62], acivicin [63], doxorubicin [63], and phenylenediamine [63] to tumor cells. 

Table 6 Considerations in the Pharmaceutical Development and Clinical Use of Both Soluble Macromolecular and Particulate Biotechnical and Site-Specific Drug-Delivery... 

V. J. Stella and K. J. Himmelstein, Critique of prodrugs and site-specific drug delivery, in Optimization of Drug Delivery, Alfred Benzon Symposium 17 (H. Bundsgaard, A. B. Hansen, and H. Kofod, eds.), Munksgaard, Copenhagen, 1982, p. 134. 

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